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Novel and potential future therapeutic options in systemic autoimmune diseases.

Autoimmune inflammation is caused by the loss of tolerance to specific self-antigens and can result in organ-specific or systemic disorders. Systemic autoimmune diseases affect a significant portion of the population with an increasing rate of incidence, which means that is essential to have effective therapies to control these chronic disorders. Unfortunately, several patients with systemic autoimmune diseases do not respond at all or just partially respond to available conventional synthetic disease-modifying antirheumatic drugs and targeted therapies. However, during the past few years, som

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… Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. (2006) 107:4907–16. doi: 10.1182/blood-2005-08-3531 77. Quartuccio L, Rupolo M, Michieli M, De Vita S. Efficacy and tolerability of repeated cycles of a once-weekly regimen of bortezomib in lupus. …

The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety

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… The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins. Mol Cell. (2015) 59:35–49. doi: 10.1016/j.molcel.2015.04.026 81. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. (1998) 67:425–79. doi: 10.1146/annurev.biochem.67.1.425 82. …

Minimal residual disease in solid tumors: Clinical applications and future directions.

Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utili

Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?

Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to

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… For example, in the development of HCC, obesity-induced insulin resistance amplifies de novo lipogenesis and increases FFA flux, which also derives from an altered gut microbiome, leading to mitochondrial dysfunction with oxidative stress, ER stress and activating the unfolded protein response, all resulting …

Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.

Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and suppressing inflammation. However, Tregs present major hurdle in eliciting potent anti-cancer immune responses. Therefore, curbing the activity of Tregs represents a novel and efficient way towards successful immunotherapy of cancer. Moreover, there is an emerging interest in harnessing Treg-based strategies for augmenting anti-cancer immunity in different types of the disease. This review summarises the crucial mechanisms of Tregs' mediated suppression of anti-cancer immunity and strategies to suppress or to

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… These effects include impaired anti-oxidant defence, ATP crunch, increased unfolded protein response (UPR), impaired regulation of cell cycle, impaired influx of calcium, inhibition of DNA repair and apotosis [ 185 ]. …

PIM1 kinase and its diverse substrate in solid tumors.

The PIM kinase family, consisting of PIM1, PIM2, and PIM3, is a group of serine/threonine protein kinases crucial for cellular growth, immunoregulation, and oncogenesis. PIM1 kinase is often overexpressed in solid and hematopoietic malignancies, promoting cell survival, proliferation, migration, and senescence by activating key genes. In vitro and in vivo studies have established the oncogenic potential of PIM1 kinases. These kinases have been implicated in tumor progression, metastasis, and resistance to chemotherapy, underscoring their potential as a therapeutic target for cancer therapy. Th

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… Inhibition of PIM1 led to increased transcription of the BH3 protein Noxa by activating the unfolded protein response, which in turn caused eIF-2α phosphorylation and elevated expression of CHOP [ 140 ]. …

Recent Advances in Therapeutics for the Treatment of Alzheimer's Disease.

The most prevalent chronic neurodegenerative illness in the world is Alzheimer's disease (AD). It results in mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial and psychological impact on the relatives of the patients. The review discusses various pathophysiological mechanisms contributing to AD, including amyloid beta, tau protein, inflammation, and other factors, while emphasizing the need for effective disease-modifying therapeutics that alter disease progression rather than merely alleviating symptoms. This review mainly covers m

AL Amyloidosis: Current Chemotherapy and Immune Therapy Treatment Strategies: JACC: CardioOncology State-of-the-Art Review.

Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as protea

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… Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells Blood 107 2006 4907 4916 16507771 10.1182/blood-2005-08-3531 PMC1895817 59 Bianchi G. Oliva L. Cascio P. …

Cancer, immune suppression and Coronavirus Disease-19 (COVID-19): Need to manage drug safety (French Society for Oncology Pharmacy [SFPO] guidelines).

The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer patients during the pandemic and aims to discuss successive issues. First we focused on the international guidelines proposing adjustments and alternative options to cancer care in order to limit hospital admission and cytopenic treatment in cancer p

Construction and validation of renal cell carcinoma tumor cell differentiation-related prognostic classification (RCC-TCDC): an integrated bioinformatic analysis and clinical study.

BackgroundRenal cell carcinoma (RCC) is a heterogeneous malignancy with diverse gene expression patterns, molecular landscapes, and differentiation characteristics of tumor cells. It is imperative to develop molecular RCC classification based on tumor cell differentiation for precise risk stratification and personalized therapy.MethodsWe obtained scRNA-seq profiles from GSE159115 and bulk RNA-seq profiles from TCGA-KIRC cohort. We then performed scRNA-seq cluster analysis, monocle2 pseudotime analysis, and prognostic analysis to obtain tumor cell differentiation-related prognostic genes (TCDGs

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… Specifically, unfolded protein response and DNA repair were notably up-regulated, while KRAS signaling dn and pancreas beta cells were notably down-regulated in metastatic RCC tumors. Figure 3. Construction and validation of the mTCDGs-based multivariable prognostic model. …

Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer.

Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases,

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut

Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.

Neuropathic pain causes plasticity in the nervous system, which is often associated with altered protein synthesis. Proteins are the key executors of cellular functions, and their alteration is closely related to the occurrence of neuropathic pain. Protein synthesis is a finely regulated process involving the interaction of multiple biomolecules. Among them, the eukaryotic translation initiation factors (eIFs) are a group of key regulatory proteins that control the initiation phase of protein translation and thus influence the rate and type of protein synthesis. Recent studies have shown that

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… Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response . FASEB J . ( 2017 ) 31 : 3868 – 81 . doi: 10.1096/fj.201700012R , PMID: 28507169 116. Milligan E Zapata V Schoeniger D Chacur M Green P Poole S . …

Tumor-Treating Fields in Glioblastomas: Past, Present, and Future.

Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of glioblastomas (GBMs), the most deadly primary brain cancer. According to on recent milestone randomized trials and subsequent observational data, TTFields therapy leads to substantially prolonged patient survival and acceptable adverse events. Clinical trials are ongoing to further evaluate the safety and efficacy of TTFields in treating GBMs and its biological and radiological correlations. TTFields is administered by delivering l

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… Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response. Pharmacol. Ther. 2018;184:13–41. doi: 10.1016/j.pharmthera.2017.10.017. 89. Da Ros M., De Gregorio V., Iorio A.L., Giunti L., Guidi M., de Martino M., Genitori L., Sardi I. …

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.

The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via r

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in expe

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flex

Окисляющие молекулярные сигнатуры в неизлечимых заболеваниях: систематический обзор комплексных подходов к машинному обучению и системной биологии.

Окисляющий стресс является одним из основных факторов патогенеза иммунных заболеваний в результате его воздействия на клеточный метаболизм, митохондриальную функцию, иммунную сигнализацию и воспалительную травму тканей. Разрушение гомеостазиса способствует метаболическому перепрограммированию и постоянной активации врожденной и адаптивной иммунной реакции, что способствует прогрессированию заболеваний через многочисленные подстрекательские и аутоиммунные расстройства. Последние достижения в области высокопроизводительных молекулярных технологий привели к созданию крупномасштабных многомерных н

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when a